This application is to continue as a participant in the collaborative multicenter prospective natural history of perinatal HIV-1 infection, the Women and Infants Transmission Study (WITS) now in the antiretroviral treatment era. The objectives of the study continue to be 1) the understanding of determinants of mother to infant HIV-1 transmission, 2) the natural history and determinants of disease progression in pediatric HIV-1 infection and 3) the effect of pregnancy on the natural history of HIV-1 infection in women. Specific objectives of WITS 3, as this initiative is called, include 1) determining mechanisms of perinatal HIV transmission and maternal cofactors related to transmission including the role of maternal drug use, the role of the placenta, the role and characteristics of HIV in the birth canal, and of maternal coinfections; 2) evaluation of factors related to successful perinatal HIV prevention strategies, with intense assessment of transmission cases that occur despite perinatal use of antiretroviral therapy; 3) determination of the impact of pregnancy on disease progression of HIV infection among women through the postpartum period, including immunologic and virologic changes in pregnant HIV-infected women who receive antiretroviral therapy during pregnancy; 4) characterization of acute HIV infection among HIV infected infants and children in light of antiretroviral, prophylactic and immune-based therapy and 5) determination of factors predicting pediatric disease progression among the cohort of HIV infected children in WITS. To this end the study will enroll annually between 30 and 40 HIV-1 infected pregnant women who agree to be followed in this history study. Information is collected on behaviors, drug use, general health, immunologic status, HIV stage of disease, HIV phenotype, HIV quantitative culture as measured bycellar infectious units per million, plasma RNA copy number, a host of lymphocyte phenotypes by flow cytometry, genital cultures including cervical lavage for HIV studies, placentas, products of conception, pediatric HIV disease status, growth and neurodevelopment. A repository of PBMC that are frozen for viability as well as of plasma is collected at every study visit for to empower the study to examine old questions with newly developed technologies as well as new scientific questions that emerge from the advancing areas of HIV basic research. The HIV infected women are followed indefinitely as are the infected children and a subset of the exposed and uninfected children. This site places particular emphasis on the understanding of the influence of hard drug use on maternal-infant HIV transmission and on pediatric disease progression that have been noted in the WITS. Characteristics of the viral phenotypes and the immune response in hard drug users compared to nondrug will be examined to better understand the mechanisms(s) for these associations and their implications for HIV-1 pathogenesis in general. Studies of compliance to perinatal transmission prevention strategies in drug using nondrug using populations as well as the examination of alternate means of ascertaining hard drug usage are also being spearheaded by this site.